F: Daudert, physician in Bad Aibiling at Rosenheim: Second International Congress
for Energy Medicine in Seefeld 1998. People with the following criteria were
used for this study: advanced cancer, people who had exhausted the usual resources
of traditional medicine and people with greatly reduced immune competent cells
(less than 50%). More than 300 patients with epithelial tumors were divided
into two groups and treated one of the two groups additionally with PEMF. The
treatment was otherwise identical for both groups (vitamin and mineral infusions,
immune stimulation, oxygen flooding therapy). The treatment was administered
for a period of two weeks with a repetition after three months. Blood tests,
which were analysed by an independent clinical laboratory, yielded comparable
values between the two groups. It was found that the buildup of the immune
system could be significantly accelerated with PEMF.

Biological effects of PEMF (pulsing electromagnetic field): an attempt to modify
cell resistance to anticancer agents.
Pulsing Electromagnetic Field (PEMF) effects lead to a modification of the multidrug
resistance (MDR) of cells in vitro and in vivo.

The murine leukemic doxorubicin-resistant cell line, P388/Dx, subjected to
PEMF irradiation in vitro, showed a significant difference in thymidine incorporation
when the concentration of doxorubicin reached a level of 1 microgram/mL, which
corresponds to the inhibition dose 50 (ID50). The human lymphoblastic leukemia
vinblastine-resistant cell line, CEM/VLB100, also showed a significant modification
under the same experimental conditions at the in vitro ID50 corresponding to
a vinblastine concentration of 100 ng/mL.

BDF1 mice transplanted with P388/Dx cells also had an increase in their life
span when doxorubicin was injected intraperitoneally in fractionated doses,
while being subjected to PEMF irradiation.

Simplicity of usage is a major feature of the IMI, as magnetic pulses pass
through all matter except certain metals. The applicator probe is held flat
against the clothing or skin of the area to be treated, and the start button
pressed. The device will begin emitting several popping noises per second (from
the arc in the plasma chamber that initiates each pulse) until the 5-minute
treatment timer turns it off. if desired, or if the probe is moved to another
location, the start button will initiate another 5minute operation for up to
four cycles, depending on the treatment protocol for a particular clinical
condition.

It is noted that in over 100,000 IMI treatments for a variety of medical problems,
no adverse effects or incidents have been reported in patients or in technicians
exposed to IMI pulses for many hundreds of hours a year.

THEORY OF OPERATION

Normal Cells

All of the many types of living cells that make up the tissues and organs
of the body are tiny electrochemical units. They are powered by a "battery*
that is continually recharged by the cells' metabolic chemistry in a closed
loop of biological energy.

We are concerned here with that battery, which consists of the membrane that
surrounds the cell. The electrical charge, or voltage across the membrane of
a normal, healthy cell varies from about 70 to 100 millivolts; this is called
the Transmembrane Potential, or TIVIP.

When a cell is poisoned, damaged, deprived of nutrients or infected, energy
is lost in fighting the problem and the TIVIP falls to a level where the cell
loses its vitality and either struggles to heal itself or dies.

Medical literature over the past few decades offers ample proof that the induction
of tiny currents of electricity is remarkably effective in healing, regenerating
and revitalizing cells damaged by trauma. Many of the earlier techniques developed
from this research involved implanting fine electrodes at the boundaries of
the injured tissue, and causing a tiny current to flow through the affected
area from low-voltage batteries. Subsequently, it was found that these healing
currents could also be induced by relatively weak magnetic devices placed close
to the trauma and kept there for days or weeks.

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Thus the healing effects of microcurrents generated or induced in the conductive
pathways of the body have been well established and this application is an
accepted clinical procedure.

There remained for Professor Pappas to discover that a weak pulsed magnetic
field, hundreds of times faster than had ever been used, applied for a millionth
of a second at a time within a frequency spectrum never before used in medical
devices, could accomplish much more within a few minutes what other stronger
magnetic induction devices required days or weeks to affect--and to do so with
much more efficient and far-reaching therapeutic results.

In short, the IMI is capable of raising the TMP of sick or damaged cells into
a normal range, thus restoring their bioenergy, facilitating the exchange of
potassium and sodium ions (the Na/K pump) and restoring their normal rate of
production of ATP which fuels the entire process. Normal healthy cells are
not adversely affected by IMI because, as in recharging any battery, the membrane-batteries
of living cells in particularly will not accept an overcharge.

Let us consider the action of the IMI in electrical terms. The massive surge
of current circulating in the applicator loop, which acts as an antenna, generates
a field of complex radiofrequency energy energy that is "broadcast" outward
in all directions normal to the direction of current flow in the loop. The
quickly expanding and collapsing pulse of magnetic energy easily penetrates
biological tissues. When a changing magnetic field intersects a conductor in
a closed circuit, it generates a current in the conductor; this is the basic
principle on which all rotary electric generators and alternators operate.
The expanding and contracting magnetic component of the pulse causes current
to flow in the many conductive paths of the body, including nerve fibers, blood
vessels (blood serum is electrically conductive) and the fluid bathing the
cells.

As the magnetic field expands through the living tissue, it induces electron
flow, or current in one direction; as it collapses, the direction is reversed.
Electrons always flow from negative (cathode) to positive (anode) potential.

The membrane itself is a dielectric that could be compared to a capacitor.
Its electrical charge is positive on the outer surface, negative on the inner
surface. Therefore such induced current polarized to push ions toward the positive
outside of the cell membrane are blocked just as no current will flow when
the positive terminals of two batteries are connected together.

Conversely, current flowing away from the membrane will pull electrons away
from it, and cause more electrons or negative ions to pile up on its interior
surface, thus incrementally increasing the charge, or potential across the
membrane and driving the TMP up towards a normal, healthy value for that cell.

This is one reason why the IMI is so quick and effective in helping damaged
cells heal. Also, although it produces no heat in the tissue, for reasons that
cannot yet be presented here it appears to increase the blood circulation around
damaged tissue. This is important, as increasing the supplies of nutrients
is also an effective aid to cell repair; this is particularly true in trauma
where circulation has been impaired by crushed or severed blood vessels or
the inflarnation and swelling that compress capillaries, blocking flow to both
the injured and uninjured cells.

Put in terms of physical chemistry, rather than biological terms, another
parallel phenomenon appears to occur: the acceleration of adencisine triphosphate
(ATP) synthesis and other aspects of the cell's biochemical anabolism. The
electrons drawn to the inner membrane by elevating the TMP increase the ionic
charge in the interior. This raises the internal degrees of freedom at a molecular
level, catalyzing dormant biochemical reactions that would not otherwise proceed
as quickly due to lack of available energy. Entropy is reduced and the cell's
metabolic rate increased, enabling the cell to heal itself and attain an optimum
functional level.

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Cancer Cells

Cancer cells grow faster, divide and multiply much more rapidly than normal
cells. As with all living cells, once their TMP falls into a critical low value,
mitosis is triggered and the cell divides into two identical copies. When the
magnetic induction action of the IMI prevents a drop in the TMP to that critical
mitosis-trigger level, the fastgrowing cancer cell cannot divide and continues
to grow larger until death occcurs.

It is clear that as a cancer cell grows at an uncontrolled rate without dividing,
the membrane is stretched thinner and thinner. When the ratio of volume to
surface area becomes too large, the membrane is unable to absorb enough nutrients
to support the bulk of the cell and starvation will result in cell death.

There are several theories about what happens to bring about cell death under
these conditions; some or all of these may apply to different types of cancer
cells.

Soft, harmless, electromagnetic treatment of cancer is quite new to medical
science, and there are still new facts to be discovered. But research continues
as new tools are developed to explore phenomena at the microscopic levels of
the molecule and the cell.

Bjorn Nordenstrom, a predminent Swedish scientist has found that cells of
cancers he has successfully treated with electrotherapy appear to become dehydrated
and die. He used an invasive surgical procedure, implanting electrodes in the
tumor to generate the microcurrents that the IMI appears to create non-invasively
by magnetic induction. His basic techniques were adopted in China where, from
1988 to 1993 over 4,000 cases of advanced malignancy were treated. Of 2516
carcinoma cases in patients over 50 years old, a 78% favorable response rate
was reported.

Dr. C.K. Chou, an American cancer researcher and his colleagues have found
that these same microcurrents alter the pH of the cancer cell and alter its
DNA so that it cannot reproduce.

In the special cases of HIV and hepatitis infections, repeated experiments
have shown that when the infected blood is treated in vitro with 50 to 100
microamperes of current, it appears to be virtually free of these viruses.
This is an exciting discovery as it suggests that the same phenomenon may occur
in the body ana raises the possibility that when an IMI device can be designed
large and powerful enough to scan or cover tne whole body in a single treatment,
these and perhaps other viral infections could be successfully conquered.

Another important aspect of the thinning membrane of a growing cancer cell
is that it becomes more porous. This appears to have two significant results.
Anticancer antibodies of the immune system can more easily penetrate the membrane
to attack the cell. Also, when electromagnetic fields are applied to the cancer,
a phenomenon known as Electroporosis develops; this permits certain pharmaceuticals
that have proven effective in chemotherapy to penetrate the membrane more quickly
and easily--allowing a significant reduction in the dosage of chemicals that
may have harmful side effects.

Bjorn Nordenstrom, a predminent Swedish scientist has found that cells of
cancers he has successfully treated with electrotherapy appear to become dehydrated
and die. He used an invasive surgical procedure, implanting electrodes in the
tumor to generate the microcurrents that the IMI appears to create non-invasively
by magnetic induction. His basic techniques were adopted in China where, from
1988 to 1993 over 4,000 cases of advanced malignancy were treated. Of 2516
carcinoma cases in patients over 50 years old, a 78% favorable response rate
was reported.

Dr. C.K. Chou, an American cancer researcher and his colleagues have found
that these same microcurrents alter the pH of the cancer cell and alter its
DNA so that it cannot reproduce.

In a laboratory study, several rodent and human cancer cell types were exposed
to permanent magnetic fields for one hour to determine what percent of the
cells would survive compared to unexposed cells. The permanent magnetic field
was extremely strong (11.6 Tesla = 116,000 gauss) and was generated by sophisticated
equipment. Some of the surviving cell fractions included 25% for human breast
carcinoma, 40% for human ovarian carcinoma, and 4% for human mouth carcinoma.
Non-Invasive permanent magnetic field modality induces lethal effects on several
rodent and human cancers.

In Vitro. Proceedings of the American Association for Cancer Research, 1994;
35, 386.

Local complications of standard intravenous injections for chemotherapy and
due to error of administration were compared in 400 patients (200 of them children)
and general wound pathologies described. Treatment for wounds included two
modalities: standard medication and alternating or pulsating magnetic field.
Magnetic therapy proved highly effective: wound healing was 3-3.5 times faster
while duration of treatment--2-3 times shorter than in standard procedure.
Clinically-verified partial adhesion-related intestinal obstruction was eliminated
by magnetic procedure in 18 children after combined treatment for lymphosarcoma
involving the ileum.

OBJECTIVE: This study was performed to clarify the usefulness of Dextran magnetite
(DM) for the oral cancer hyperthermia.

METHODS: Tumors were induced in golden hamster tongue by 9,10-dimethyl 1-1,2-benzanthracene
(DMBA) application. DM suspension was locally injected into the tumor-bearing
tongue and tongues were heated up to 43.0-45.0 degrees C, by AC magnetic field
of 500 kHz.

RESULTS: The average time taken for the temperature to rise to 43.0 degrees
C or above was 162 s (n = 17) at the margin of the tumor and 420 s (n = 17)
at the center of the tumor. According to the tumor volume, the time required
for an increase in the central temperature of tumor to 43.0 degrees C tended
to be prolonged. Both temperatures could be maintained at approximately 43.0-45.0
degrees C for 30 min. The inhibition of the growth of tongue carcinoma in the
four-time heating group was significantly greater than in the control group
(P < 0.01). Moreover, the survival rate was significantly higher in the
heated groups than in the control group (P < 0.01). Histological examination
revealed a brown uniform DM accumulation at the stroma in the margin of the
tumors. Many of tumor cells disappeared at the site adjacent to this accumulation.

CONCLUSION: These results strongly suggest the usefulness of this local hyperthermic
system in the oral region that is accessible to this treatment.

We have completed the lowest level of exposure in a Phase I study, designed
to establish the safety and toxicity of the combination of a static magnetic
field (SMF) and antineoplastic chemotherapy in patients with advanced malignancy.
The SMF application is carefully controlled by applying the magnet to the patient
only in our clinic during chemotherapy administration. No increase in the severity
of chemotherapy toxicity as measured by white blood cell count and platelet
count was seen in the participants exposed to SMF compared to the historical
control subjects. These data have permitted the next group of subjects to be
treated at the next dose level. Published 2003 Wiley-Liss, Inc.

OBJECTIVE: To investigate the effect of magnetic doxorubicin liposome (MDL)
in the targeting treatment of nude mice bearing colon cancer.

METHODS: Human colon cancer line LoVo cells were implanted hypodermically
into nude mouse. Two weeks after the mouse was killed and the tumor was taken
out and cut into small pieces to be retransplanted into nude mice so as to
establish an experimental model. MDL was prepared by reverse-phase evaporation
method. The particle size and structure of MDL were evaluated. Eighteen nude
mice with colon cancer were divided into 3 groups of 3 mice: free DOX group,
MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+)
group (magnetic field with the strength of 4 500 G was added). DOX of the dosage
of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the
mice were killed 30 minutes after. Fluorescence spectrophotometry was used
to examine the concentrations of DOX in the tissues and plasma. Another 36
nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline
group (as controls), DOX group, blank liposome group, magnetic liposome group,
MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+)
group (rare earth magnet was implanted into the tumor). The body weight, longest
diameter of tumor, and short diameter vertical to the longest diameter were
calculated regularly. The mice were killed 11 days after. The tumors were taken
out to undergo staining and light microscopy. Flow cytometry was used to examine
the apoptosis of tumor cells.

RESULTS: The particle size of MDL was 230 nm and the magnetic particles (Fe(3)O(4))
were evenly distributed within the liposome. The DOX concentration in tumor
tissue of the MDL (+) group was remarkably higher than those of the DOX and
MDL (-) groups (both P < 0.05). The DOX concentration in heart and kidney
of the DOX group were higher than those of the other 2 groups, and the plasma
DOX concentrations of the DOX group was significantly lower than those of the
other groups (all P < 0.05). The growth speed of tumor in the MDL (+) group
was significantly lower, and the tumor weight was significantly less than in
other groups.

CONCLUSION: Magnetic doxorubicin liposome, as a carrier of anticancer drug,
has a good targeting function toward the magnetite and has a significant anticancer
effect.

Heat shock proteins (HSPs) are recognized as significant participants in immune
reactions. We previously reported that expression of HSP70 in response to hyperthermia,
produced using our original magnetite cationic liposomes (MCLs), induces antitumor
immunity. In the present study, we examine whether the antitumor immunity induced
by hyperthermia is enhanced by hsp70 gene transfer. A human hsp70 gene mediated
by cationic liposomes was injected into a B16 melanoma nodule in C57BL/6 mice
in situ. At 24 hours after the injection of the hsp70 gene, MCLs were injected
into melanoma nodules in C57BL/6 mice, which were subjected to an alternating
magnetic field for 30 minutes. The temperature at the tumor reached 43 degrees
C and was maintained by controlling the magnetic field intensity. The combined
treatment strongly arrested tumor growth over a 30-day period, and complete
regression of tumors was observed in 30% (3/10) of mice. Systemic antitumor
immunity was induced in the cured mice. This study demonstrates that this novel
therapeutic strategy combining the use of hsp70 gene therapy and hyperthermia
using MCLs may be applicable to patients with advanced malignancies.

Superparamagnetic as well as fine ferrimagnetic particles such as Fe_{3}O_{4},
have been extensively used in magnetic field induced localized hyperthermia
for the treatment of cancer. The magnetic materials with Curie temperature
(T_c) between 42 and 50 degrees C, with sufficient biocompatibility are the
best candidates for effective treatment such that during therapy it acts as
in vivo temperature control switch and thus over heating could be avoided.
Ultrafine particles of substituted ferrite Co_{1-a}Zn_{a}Fe_{2}O_{4} and substituted
yttrium-iron garnet Y_{3}Fe_{5-x}Al_{x}O_{12} have been prepared through microwave
refluxing and citrate-gel route respectively. Single-phase compounds were obtained
with particle size below 100 nm. In order to make these magnetic nano particles
biocompatible, we have attempted to coat these above said composition by alumina.
The coating of alumina was done by hydrolysis method. The coating of hydrous
aluminium oxide has been done over the magnetic particles by aging the preformed
solid particles in the solution of aluminium sulfate and formamide at elevated
temperatures. In vitro study is carried out to verify the innocuousness of
coated materials towards cells. In vitro biocompatibility study has been carried
out by cell culture method for a period of three days using human WBC cell
lines. Study of cell counts and SEM images indicates the cells viability/growth.
The in vitro experiments show that the coated materials are biocompatible.

Heat shock proteins (HSPs) are recognized as significant participants in cancer
immunity. We previously reported that HSP70 expression following hyperthermia
using magnetic nanoparticles induces antitumor immunity. In the present study,
we examine whether the antitumor immunity induced by hyperthermia is enhanced
by administration of recombinant HSP70 protein into the tumor in situ. Hyperthermia
was conducted using our original magnetite cationic liposomes (MCLs), which
have a positive surface charge and generate heat in an alternating magnetic
field (AMF) due to hysteresis loss. MCLs and recombinant mouse HSP70 (rmHSP70)
were injected into melanoma nodules in C57BL/6 mice, which were subjected to
AMF for 30 min. Temperature within the tumor reached 43 degrees C and was maintained
by controlling the magnetic field intensity. The combined treatment strongly
inhibited tumor growth over a 30-day period and complete regression of tumors
was observed in 20% (2/10) of mice. It was also found that systemic antitumor
immunity was induced in the cured mice. This study suggests that novel combined
therapy using exogenous HSP70 and hyperthermia has great potential in cancer
treatment.

We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627-3633,
1999) that power-line frequency (50-Hz) magnetic fields (MFs) at micro T-flux
densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene
(DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated
that MF exposure results in an enhanced proliferative activity of the mammary
epithelium of SD rats (M. Fedrowitz et al., Cancer Res., 62: 1356-1363, 2002),
which is a likely explanation for the cocarcinogenic or tumor-promoting effects
of MF exposure in the DMBA model. However, in contrast with our data, in a
similar study conducted by Battelle in the United States, no evidence for a
cocarcinogenic or tumor-promoting effect of MF exposure was found in the DMBA
model in SD rats (L. E. Anderson et al., Carcinogenesis, 20: 1615-1620, 1999).
Probably the most important difference between our and the Battelle studies
was the use of different substrains of SD rats; the United States rats were
much more susceptible to DMBA than the rats used in our studies. This prompted
us to compare different substrains of SD outbred rats in our laboratory in
respect to MF effects on cell proliferation in the mammary gland, susceptibility
to DMBA-induced mammary cancer, and MF effects on mammary tumor development
and growth in the DMBA model. The SD substrain (termed "SD1") used
in all of our previous studies was considered MF-sensitive and used for comparison
with another substrain ("SD2") obtained from the same breeder. In
contrast with SD1 rats, no enhanced cell proliferation was determined after
MF exposure in SD2 rats. MF exposure significantly increased mammary tumor
development and growth in SD1 but not SD2 rats. These data indicate that the
genetic background plays a pivotal role in effects of MF exposure. Different
strains or substrains of rats may serve to evaluate the genetic factors underlying
sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure.

Departments of Radiology and Medicine, University of California, San Francisco,
505 Parnassus Avenue, Room M-361, San Francisco, CA 94143.

Four patients with inoperable hepatocellular carcinoma were treated with a
magnetic targeted carrier bound to doxorubicin (MTC-DOX) by using a joint magnetic
resonance (MR) imaging/conventional angiography system consisting of a 1.5-T
short-bore magnet connected to a C-arm angiography unit by a sliding tabletop.
Selective transcatheter delivery of the MTC-DOX to the hepatic artery was monitored
by using intraprocedural MR imaging, and interim catheter manipulation was
performed with fluoroscopic guidance to optimize agent delivery to the tumor
and minimize delivery to normal tissue. The final fraction of treated tumor
volume ranged from 0.64 to 0.91. The fraction of affected normal liver volume
ranged from 0.07 to 0.30. The dual MR imaging/conventional angiography system
shows promise for directing magnetically targeted tumor therapies. Copyright
RSNA, 2004

Basic principles of a novel method of cancer treatment are explained. Method
is based on the thermal activation of an inactive prodrug encapsulated in magnetoliposomes
via Neel and Brown effects of inductive heating of subdomain superparamagnetic
particles to sufficiently high temperatures. This principle may be combined
with targeted drug delivery (using constant magnetic field) and controlled
release (using high-frequency magnetic field) of an activated drug entrapped
in magnetoliposomes. Using this method drug may be applied very selectively
in the particular site of organism and this procedure may be repeated several
times using e.g. stealth magnetoliposomes which are circulating in a blood-stream
for several days. Moreover the magnetoliposomes concentrated by external constant
magnetic field in tumor vasculature may lead to embolic lesions and necrosis
of a tumor body and further the heat produced for thermal activation of a drug
enhances the effect of chemotherapy by local hyperthermic treatment of neoplastic
cells.

The development of an active drug delivery system is an attractive approach
to increase the targetability of anticancer agents. In the present study, we
examined the efficiency of systemic chemotherapy with small magnetic liposomes
containing doxorubicin (magnetic DOX liposomes) and an externally applied electromagnetic
force in osteosarcoma-bearing hamsters. Syrian male hamsters inoculated with
osteosarcoma, OS515, in the limb were studied 7 days after inoculation. The
efficiency of this system was evaluated by measuring the tissue distribution
and tumor-suppressing effects of DOX on primary tumor growth and lung metastases.
A DC dipole electromagnet was used, and the hamster's tumor-bearing limb was
placed between 2 poles after the i.v. administration of liposomes. The dose
of DOX and the magnetic field strength were fixed at 5 mg/kg and 0.4 T, respectively.
Administration of magnetic DOX liposomes followed by 60 min application of
magnetic field produced a 3- to 4-fold higher maximum DOX concentration in
the tumor. This newly designed systemic chemotherapy significantly suppressed
primary tumor growth for at least 2 weeks, though other DOX treatments also
suppressed compared to control. Histologic examination confirmed a greater
antitumor effect of this systemic chemotherapy compared to standard methods.
In addition, this approach significantly suppressed lung metastases measured
at 3 weeks posttreatment. These results suggest that this systemic chemotherapy
can effectively reduce primary tumor growth and suppress lung metastasis due
to increased targeting of DOX. Such targeted drug delivery for anticancer agents
would provide clinical advantages compared to current methods. Copyright 2004
Wiley-Liss, Inc.